Parameterized hemodynamic response function data of healthy individuals obtained from resting-state functional MRI in a 7T MRI scanner

Functional magnetic resonance imaging (fMRI), being an indirect measure of brain activity, is mathematically defined as a convolution of the unmeasured latent neural signal and the hemodynamic response function (HRF). The HRF is known to vary across the brain and across individuals, and it is modulated by neural as well as non-neural factors. Three parameters characterize the shape of the HRF, which is obtained by performing deconvolution on resting-state fMRI data: response height, time-to-peak and full-width at half-max. The data provided here, obtained from 47 healthy adults, contains these three HRF parameters at every voxel in the brain, as well as HRF parameters from the default-mode network (DMN). In addition, we have provided functional connectivity (FC) data from the same DMN regions, obtained for two cases: data with deconvolution (HRF variability minimized) and data with no deconvolution (HRF variability corrupted). This would enable researchers to compare regional changes in HRF with corresponding FC differences, to assess the impact of HRF variability on FC. Importantly, the data was obtained in a 7T MRI scanner. While most fMRI studies are conducted at lower field strengths, like 3T, ours is the first study to report HRF data obtained at 7T. FMRI data at ultra-high fields contains larger contributions from small vessels, consequently HRF variability is lower for small vessels at higher field strengths. This implies that findings made from this data would be more conservative than from data acquired at lower fields, such as 3T. Results obtained with this data and further interpretations are available in our recent research study (Rangaprakash et al., in press) [1]. This is a valuable dataset for studying HRF variability in conjunction with FC, and for developing the HRF profile in healthy individuals, which would have direct implications for fMRI data analysis, especially resting-state connectivity modeling. This is the first public HRF data at 7T

Brain Connectivity Networks for the Study of Nonlinear Dynamics and Phase Synchrony in Epilepsy

Assessing complex brain activity as a function of the type of epilepsy and in the context of the 3D source of seizure onset remains a critical and challenging endeavor. In this dissertation, we tried to extract the attributes of the epileptic brain by looking at the modular interactions from scalp electroencephalography (EEG). A classification algorithm is proposed for the connectivity-based separation of interictal epileptic EEG from normal. Connectivity patterns of interictal epileptic discharges were investigated in different types of epilepsy, and the relation between patterns and the epileptogenic zone are also explored in focal epilepsy. A nonlinear recurrence-based method is applied to scalp EEG recordings to obtain connectivity maps using phase synchronization attributes. The pairwise connectivity measure is obtained from time domain data without any conversion to the frequency domain. The phase coupling value, which indicates the broadband interdependence of input data, is utilized for the graph theory interpretation of local and global assessment of connectivity activities. The method is applied to the population of pediatric individuals to delineate the epileptic cases from normal controls. A probabilistic approach proved a significant difference between the two groups by successfully separating the individuals with an accuracy of 92.8%. The investigation of connectivity patterns of the interictal epileptic discharges (IED), which were originated from focal and generalized seizures, was resulted in a significant difference ( ) in connectivity matrices. It was observed that the functional connectivity maps of focal IED showed local activities while generalized cases showed global activated areas. The investigation of connectivity maps that resulted from temporal lobe epilepsy individuals has shown the temporal and frontal areas as the most affected regions. In general, functional connectivity measures are considered higher order attributes that helped the delineation of epileptic individuals in the classification process. The functional connectivity patterns of interictal activities can hence serve as indicators of the seizure type and also specify the irritated regions in focal epilepsy. These findings can indeed enhance the diagnosis process in context to the type of epilepsy and effects of relative location of the 3D source of seizure onset on other brain areas

Complexity of functional connectivity networks in mild cognitive impairment subjects during a working memory task

Objectives: The objective is to study the changes of brain activity in patients with mild cognitive impairment (MCI). Using magneto-encephalogram (MEG) signals, the authors investigate differences of complexity of functional connectivity network between MCI and normal elderly subjects during a working memory task. Methods: MEGs are obtained from 18 right handed patients with MCI and 19 age-matched elderly participants without cognitive impairment used as the control group. The brain networks’ complexities are measured by Graph Index Complexity (Cr) and Efficiency Complexity (Ce). Results: The results obtained by both measurements show complexity of functional networks involved in the working memory function in MCI subjects is reduced at alpha and theta bands compared with subjects with control subjects, and at the theta band this reduction is more pronounced in the whole brain and intra left hemisphere. Conclusions: Ce would be a better measurement for showing the global differences between normal and MCI brains compared with Cr. Significance: The high accuracy of the classification shows Ce at theta band can be used as an index for assessing deficits associated with working memory, a good biomarker for diagnosis of MC

Brain electrical activity discriminant analysis using Reproducing Kernel Hilbert spaces

A deep an adequate understanding of the human brain functions has been an objective for interdisciplinar teams of scientists. Different types of technological acquisition methodologies, allow to capture some particular data that is related with brain activity. Commonly, the more used strategies are related with the brain electrical activity, where reflected neuronal interactions are reflected in the scalp and obtained via electrode arrays as time series. The processing of this type of brain electrical activity (BEA) data, poses some challenges that should be addressed carefully due their intrinsic properties. BEA in known to have a nonstationaty behavior and a high degree of variability dependenig of the stimulus or responses that are being adressed..

Assessment of a multi-measure functional connectivity approach

Efforts to find differences in brain activity patterns of subjects with neurological and psychiatric disorders that could help in their diagnosis and prognosis have been increasing in recent years and promise to revolutionise clinical practice and our understanding of such illnesses in the future. Resting-state functional magnetic resonance imaging (rsfMRI) data has been increasingly used to evaluate said activity and to characterize the connectivity between distinct brain regions, commonly organized in functional connectivity (FC) matrices. Here, machine learning methods were used to assess the extent to which multiple FC matrices, each determined with a different statistical method, could change classification performance relative to when only one matrix is used, as is common practice. Used statistical methods include correlation, coherence, mutual information, transfer entropy and non-linear correlation, as implemented in the MULAN toolbox. Classification was made using random forests and support vector machine (SVM) classifiers. Besides the previously mentioned objective, this study had three other goals: to individually investigate which of these statistical methods yielded better classification performances, to confirm the importance of the blood-oxygen-level-dependent (BOLD) signal in the frequency range 0.009-0.08 Hz for FC based classifications as well as to assess the impact of feature selection in SVM classifiers. Publicly available rs-fMRI data from the Addiction Connectome Preprocessed Initiative (ACPI) and the ADHD-200 databases was used to perform classification of controls vs subjects with Attention-Deficit/Hyperactivity Disorder (ADHD). Maximum accuracy and macro-averaged f-measure values of 0.744 and 0.677 were respectively achieved in the ACPI dataset and of 0.678 and 0.648 in the ADHD-200 dataset. Results show that combining matrices could significantly improve classification accuracy and macro-averaged f-measure if feature selection is made. Also, the results of this study suggest that mutual information methods might play an important role in FC based classifications, at least when classifying subjects with ADHD

Modelling and quantifying brain connectivity and dynamics with applications in aging and ADHD

Human brain is a complex organ and made up of integrative networks encompassing a large number of regions. These regions communicate with each other to share information involved in complex cognitive processes. Functional connectivity (FC) represents the level of synchronization between different brain regions/networks. Studying functional interactions of the brain creates a platform for understanding functional architecture of the brain as an integrative network and has implications for understanding human cognition. Furthermore, there is evidence that FC patterns are sensitive to different diseases. In addition, age is a significant determinant of intra-/inter-individual variability in the FC patterns. Therefore, key aims for the studies included in this thesis were to apply and develop novel resting-state FC methodologies, with applications in healthy aging and ADHD. Indeed, measures of the brain’s FC may serve as a useful tool to diagnose and predict the course of disease, and useful in developing individualized therapies. Age- or disease-related alterations in the FC could reflect a multitude of factors, including changes in structural connectivity. However, we still have limited knowledge of the emergence of brain dynamics from the underlying anatomy. The interplay between the brain’s structure and dynamics underlies all brain functions. Therefore, in the last study we focused on the systematic modeling of the brain network dynamics. Large-scale computational models are uniquely suited to address difficult questions related to the role of brain’s structural network in shaping functional interactions. In addition, computational modeling of the brain enables us to test different hypotheses without any experimental complication while it provides us with a platform for improving our understanding of different brain mechanisms. A new macroscopic computational model of the brain oscillations for resting-state fMRI was introduced in this thesis, which outperforms previous model in the same class. Then, the effects of malfunctions in different brain regions were simulated and subsequently predicted perturbation patterns were recruited for local vulnerability mapping as well as quantification of hazard rates induced after perturbing any brain regio

Functional integration in the cortical neuronal network of conscious and anesthetized animals

General anesthesia consists of amnesia, analgesia, areflexia and unconsciousness. How anesthetics suppress consciousness has been a mystery for more than one and a half centuries. The overall goal of my research has been to determine the neural correlates of anesthetic-induced loss of consciousness. I hypothesized that anesthetics induce unconsciousness by interfering with the functional connectivity of neuronal networks of the brain and consequently, reducing the brain\u27s capacity for information processing. To test this hypothesis, I performed experiments in which neuronal spiking activity was measured with chronically implanted microelectrode arrays in the visual cortex of freely-moving rats during wakefulness and at graded levels of anesthesia produced by the inhalational anesthetic agent desflurane. I then applied linear and non-parametric information-theoretic analyses to quantify the concentration-dependent effect of general anesthetics on spontaneous and visually evoked spike firing activity in rat primary visual cortex. Results suggest that desflurane anesthesia disrupts cortical neuronal integration as measured by monosynaptic connectivity, spike burst coherence and information capacity. This research furthers our understanding of the mechanisms involved with the anesthetic-induced LOC which may facilitate in the development of better anesthetic monitoring devices and the creation of effective anesthetic agents that will be free of unwanted side effects

Dynamic Adaptation of Brain Networks from Rest to Task and Application to Stroke Research

Examining how motor task modulates brain activity plays a critical role of understanding how cerebral motor system works and could further be applied in the research of motor disability due to neurological diseases. Recent advances in neuroimaging have resulted in numerous studies focusing on motor-induced modulation of brain activity and most widely used strategy of these studies was identifying activated brain regions during motor task through event-related/block-design experiment paradigms. Despite progress obtained, motor-related activation analysis mainly focused on modulation of brain activities for individual brain regions. However, human brain is known to be an integrated network, and the adaptation of brain in response to motor task could be reflected by the modulation of brain networks. Thus, investigating the spatiotemporal modulation of task-state brain networks during motor task would provide system-level information regarding the underlying adaptation of cerebral motor system in response to the motor task and could be further applied in the research of motor disability due to neurological diseases. Although the task-state functional connectivity (FC) and networks have been examined by previous studies, there are still several aspects needed to be explored: (1) Previous task-state FC studies were mainly based on functional magnetic resonance imaging (fMRI) and potential of applying functional near-infrared spectroscopy (fNIRS), which is a promising complementary modality to fMRI because of its low cost and relatively high temporal resolution (10 Hz in sampling rate compared with less than 1Hz in sampling rate for fMRI), in task-state FC studies should be explored. (2) In the fMRI studies, the task-state brain network was mainly investigated from the perspective of static FC, which focuses on the spatial pattern of the task-state brain networks. However, brain activities and cognitive processes are known to be dynamic and adaptive and the newly emerging dynamic FC analysis could further provide temporal patterns of the task-state brain networks. Thus, the spatiotemporal pattern of task-state brain network during motor task is still needed to be investigated by dynamic FC analysis based on fMRI; (3) Task-state brain network analysis has not been applied in the research of stroke, and the relationship between task-state brain network and stroke recovery has not been investigated; Therefore, in this thesis, we aim to investigate the task-state brain networks during motor task using both static and dynamic FC analysis based on fNIRS and fMRI to reveal the motor task-specific spatiotemporal changes of brain networks compared with resting conditions, and further applied the task-state brain network analysis in the research of stroke recovery In this thesis, fMRI and fNIRS were employed to record the brain hemodynamic signals, and static FC and dynamic FC were used to investigate spatiotemporal pattern of task-state brain network during motor task. In addition, the fMRI data of stroke patients were recorded at four time points post stroke, and the reorganization of task-state brain network as well as its relationship to stroke recovery were examined. Specific results are described as follow: (1) Through static FC analysis of fNIRS during rest and motor preparation, increased FC were identified during motor preparation, especially the FC connecting right dorsolateral prefrontal cortex (DLPFC) with contralateral primary somatosensory cortex (S1) and primary motor cortex (M1) as well as the FC connecting contralateral S1 with ipsilateral S1 and M1. Channels located in sensorimotor networks and right DLPFC were also found activated during motor preparation. Our findings demonstrated that the sensorimotor network was interacting with high-level cognitive brain network to maintain the motor preparation state. (2) Through dynamic FC analysis of fNIRS during rest and motor execution, increased variability of FC connecting contralateral premotor and supplementary motor cortex (PMSMC) and M1 was identified, and the nodal strength variability of these two brain regions were also increased during motor execution. Our findings demonstrated that contralateral M1 and PMSMC were interacting with each other actively and dynamically to facilitate the fist opening and closing. (3) Through dynamic FC analysis on fMRI data, two principal FC states during rest and one principal FC state during motor task were identified. The 1st principal FC state in rest was similar to that in task, which likely represented intrinsic network architecture and validated the broadly similar spatial patterns between rest and task. However, the presence of a 2nd principal FC state with increased FC between default-mode network (DMN) and motor network (MN) in rest with shorter "dwell time" could imply the transient functional relationship between DMN and MN to establish the "default mode" for motor system. In addition, the more frequent shifting between two principal FC states in rest indicated that the brain networks dynamically maintained the "default mode" for the motor system. In contrast, during task, the presence of a single principal FC state and reduced FC variability implied a more temporally stable connectivity, validating the distinct temporal patterns between rest and task. Our findings suggested that the principal states could show a link between the rest and task states, and verified our hypothesis on overall spatial similarity but distinct temporal patterns of dynamic brain networks between rest and task states. (4) Task-state motor network was applied in the research of motor disability due to stroke and topological reorganization of task-state motor network was identified during sub-acute phase post stroke. In addition, for the first time, our study found the topological configuration of task-state motor network at the early recovery stage were capable of predicting the motor function restoration during sub-acute phase. In general, the findings demonstrated the reorganization and potential prognostic value of task-state brain network after stroke, which provided new insights into understanding the brain reorganization and stroke rehabilitation. In summary, this thesis used two neuroimaging modalities (fMRI and fNIRS) to investigate how brain networks, especially the motor network and high-level cognitive network, would reorganize spatiotemporally from resting-state to motor tasks through both static and dynamic FC analysis, and further applied the task-state brain network analysis in the research of motor disability due to stroke. Our findings revealed the underlying spatiotemporal adaptation of brain networks in response to motor task and demonstrated the potential clinical prognostic value of task-state motor network during stroke recovery. The novelties of this thesis are as follow: (1) dynamic FC was innovatively applied in revealing the motor task-specific spatiotemporal changes of brain networks compared with resting conditions; (2) task-state motor network was applied in the research of stroke recovery; (3) static and dynamic FC analysis were innovatively applied in fNIRS data.Ph.D., Biomedical Engineering -- Drexel University, 201